SFRP4(+)IGFBP5(hi) NKT cells induced neural-like cell differentiation to contribute to adenomyosis pain.

SFRP4(+)IGFBP5(hi) NKT cells induced neural-like cell differentiation to contribute to adenomyosis pain.
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SFRP4 IGFBP5 hi NKT 细胞诱导神经样细胞分化,从而导致子宫腺肌病疼痛。

DOI:
10.3389/fimmu.2022.945504
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发表时间:
2022
影响因子:
7.3
通讯作者:
--
中科院分区:
医学2区
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子宫腺肌病是一种雌激素依赖性妇科疾病。慢性疼痛是子宫腺肌病的主要临床症状,其发病机制至今尚未明确。作为具有T细胞和自然杀伤(NK)细胞特性的组合淋巴细胞,NK T(NKT)细胞在针对许多疾病的免疫防御中发挥作用并调节细胞分化。本研究通过单细胞测序分析了子宫腺肌病伴或不伴疼痛的组织细胞样本。我们在子宫腺肌病疼痛组中发现了一个特殊的分泌型卷曲相关蛋白4(SFRP 4)+NKT细胞群和大量未分化的多能干细胞。我们发现SFRP 4 +NKT细胞中IGFBP5的高表达可以促进多能干细胞通过单细胞轨迹分化为神经样细胞。通过样本验证,我们发现神经元标记物NEFM的表达程度与子宫腺肌病患者疼痛持续时间相关。IGFBP5的表达与子宫腺肌病患者疼痛评分呈正相关。总的来说,这些发现表明SFRP 4 +IGFBP5hi NKT细胞能够将部分干细胞转化为神经源性细胞并诱导子宫腺肌病疼痛。
Adenomyosis is an estrogen-dependent gynecological disease. The pathogenesis of chronic pain, the main clinical symptom of adenomyosis, remains undefined. As a combination lymphocyte with both T-cell and natural killer (NK)–cell properties, NK T (NKT) cells play a role in immune defense against numerous diseases and modulate cell differentiation. This study analyzed the tissue-cell samples from adenomyosis with or without pain by single-cell sequencing. We found a specific population of secreted frizzled-related protein 4 (SFRP4)+NKT cells and a large amount of undifferentiated multipotent stem cells in the adenomyosis pain group. We discovered that a high expression of IGFBP5 in SFRP4+NKT cells could promote the differentiation of multipotent stem cells into neural-like cells via the single-cell trajectory. Through verification by the sample, we found that the degree of the expression of the neuronal marker NEFM was correlated with the duration of pain in adenomyosis patients. The expression of IGFBP5 was positively correlated with the pain scores of adenomyosis patients. Collectively, these findings suggest that SFRP4+IGFBP5hi NKT cells were capable of converting part of the stem cells into neurogenic cells and inducing adenomyosis pain.
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